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ZIOPHARM Announces Clinical Data Highlighting Favorable Interim Survival Results with Gene Therapy Candidate Ad-RTS-hIL-12 in Brain Cancer
— Data to be Presented at the 2016 ASCO Annual Meeting —
— Company to Discuss Results with Regulators after Additional Follow Up —
BOSTON, May 18, 2016 (GLOBE NEWSWIRE) -- ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) today announced that interim results from the Company's ongoing Phase 1, multi-center dose-escalation study of the gene therapy candidate Ad-RTS-hIL-12 + orally-administered veledimex in patients with recurrent or progressive glioblastoma will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting held June 3-7, 2016, at McCormick Place in Chicago, Illinois. Ad-RTS-hIL-12 + veledimex is a novel viral gene therapy candidate for the controlled expression of interleukin 12 (IL-12), a pro-inflammatory cytokine critical for stimulating anti-cancer immune responses.
Glioblastoma is an aggressive primary brain tumor affecting approximately 74,000 people worldwide each year.i, ii Recurrent glioblastoma is an aggressive cancer with one of the lowest 3-year survival rates, at 3%, among all cancers.iii For patients who have experienced multiple recurrences the prognosis is particularly poor, with a median overall survival (OS) of 6-7 months, while OS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is approximately 3-5 months.iv, v
The primary objective of the study is to determine the safety and tolerability of a single intratumoral Ad-RTS-hIL-12 injection activated upon dosing with oral veledimex. Secondary objectives are to determine the Ad-RTS-hIL-12 + veledimex maximum tolerated dose, the immune responses elicited by Ad-RTS-hIL-12 + veledimex, and assessment of biologic response. Eleven patients with recurrent high-grade gliomas (one with grade III and ten with grade IV) have been treated to date with Ad-RTS-hIL-12 through direct injection into their brain tumors, including seven patients in the first dose cohort (veledimex dosed at 20 mg) and four in the ongoing second dose cohort (veledimex dosed at 40 mg). Veledimex was taken orally to activate the production of IL-12 from the tumor site and stimulate an immune response.
Patients enrolled in this multi-center study have all failed standard therapy, with nine of eleven patients failing additional salvage treatments, for a mean of 2.7 prior lines of therapy in cohort one and 2.0 prior lines in cohort two. No enrollment restrictions were placed on tumor size or location within the supratentorial space. Overall median follow-up for patients enrolled in the trial is 6.2 months with 10 of 11 alive. In the fully-enrolled cohort one, 6 of 7 (86%) patients remain alive with a median follow up of 6.8 months. Enrollment in cohort two is ongoing. Even at its lowest dose, the presence of IL-12 in the bloodstream could be detected, demonstrating that veledimex is bioavailable and crosses the blood brain barrier at sufficient levels to turn on the RheoSwitch (RTS®) and generate IL-12, which could be measured in the blood stream. Furthermore, for those patients that experienced adverse events associated with the treatment, discontinuing veledimex reversed these adverse events.
"Early results observed in the limited number of patients who have been treated with Ad-RTS-hIL-12 + veledimex are very encouraging for a Phase 1 study," said Ennio Antonio Chiocca, M.D., Ph.D., Harvey W. Cushing Professor of Neurosurgery, Department of Surgery, Harvard Medical School, Surgical Director, Center for Neuro-oncology, Dana-Farber Cancer Institute, Chairman, Neurosurgery, Brigham And Women's Hospital and Co-Director, Institute for the Neurosciences, Brigham And Women's Hospital. "Virus-based gene therapy used to stimulate an immunological response in the brain is at the frontier of innovation in treatment, with Ad-RTS-hIL-12 offering perhaps the most controllable approach within this field. In this study, we see encouraging signs of immune activation following the administration of Ad-RTS-hIL-12 + veledimex."
Overall Ad-RTS-hIL-12 + veledimex was well tolerated. All serious adverse events and Grade 3 related toxicities were rapidly reversible upon discontinuation of veledimex. The most common related adverse events included headache, nausea/vomiting, fever, white blood cell/leukocyte count decrease, platelet count decrease and liver function test increase. Four subjects had related serious adverse events.
"Because the brain is a segregated and fragile environment, the ability to turn an immune response on and off is critical to balancing efficacy and tolerability," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "As we continue to follow patients with extremely guarded prognoses in this multi-center trial, we hope that these promising early trends in survival are maintained. Our goal, once we reach an optimal dose, will be to promptly initiate registration trial discussions with regulators."
Dr. Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM, added: "Basing our approach on the genetic engineering of adenovirus offers a simpler strategy than replicating viral-therapy options, one that can be rapidly controlled via a drug activating a gene switch, and one that does not rely on intratumoral catheterization. We look forward to testing Ad-RTS-hIL-12 + veledimex not just on its own, but in combination with other immuno-oncology approaches, including checkpoint inhibitors and natural killer cells, in clinical trials that we plan to start this year and next. Our data suggest that patients can take a drug by mouth to activate the immune response in their tumors with exciting results."
Ad-RTS-hIL-12 + veledimex has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with malignant glioma.
ASCO Presentation Details
Title: Effect of controlled intratumoral viral delivery of Ad-RTS-hIL-12 + oral veledimex in subjects with recurrent or progressive glioma
Poster Session: Central Nervous System Tumors
Date and Time: Saturday, June 4, 2016 1:00 PM — 4:30 PM CT
Abstract Number: 2052
Poster: #239
Location: Hall A
In addition to the GBM study, a study design for the Company's Phase 1b/2 clinical trial of Ad-RTS-hIL-12 + veledimex in locally advanced or metastatic breast cancer will be outlined at the ASCO annual meeting. The study, which is being conducted at the Memorial Sloan Kettering Cancer Center in New York, is designed to examine the safety, tolerability and efficacy of Ad-RTS-hIL-12 immunotherapy given following standard of care chemotherapy in up to 40 women with locally advanced or metastatic breast cancer of all subtypes. The Company expects that outcome data from this study will be presented at a scientific meeting in the second half of the year.
Title: Phase 1b/2 study of intratumoral Ad-RTS-hIL-12 + veledimex in patients with chemotherapy-responsive locally advanced or metastatic breast cancer
Poster Session: Developmental Therapeutics—Immunotherapy
Date and Time: Sunday, June 5, 2016 8:00 AM — 11:30 AM CT
Abstract Number: TPS3097
Poster: #418a
Location: Hall A
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